Cerebral tryptophan metabolism, which is known to affect Mycobacterium tuberculosis growth and CNS inflammation, is important for the outcome of tuberculous meningitis. CSF tryptophan concentrations in tuberculous meningitis are under strong genetic influence, probably contributing to the variable outcomes of tuberculous meningitis. Interventions targeting tryptophan metabolism could improve outcomes of tuberculous meningitis.

Despite devastating mortality among patients with tuberculosis meningitis, little progress has been made in understanding the pathophysiology of this disease since the landmark autopsy studies of Rich and McCordick in the 1930s.1 Even with treatment, two-thirds of patients die or are left with severe neurological deficits, including cognitive impairment, epilepsy, and paralysis.2 In The Lancet Infectious Diseases, Arjan van Laarhoven and colleagues3 present an elegant systems biology (or multi-omics) approach designed to elucidate the underlying mechanisms that cause these dire outcomes and ultimately aiming to identify new approaches to therapeutics.

3. A Prospective Evaluation of a multisite Cryptococcal Screening and Treatment program in HIV clinics in Uganda

AbstractBackground:Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset, and predicts death. CrAg screening amongst those with advanced HIV, and treatment of those CrAg+ with fluconazole has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside of clinical trials.Methods:We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff. We evaluated programmatic implementation, including time to initiation of fluconazole, time to initiation of antiretroviral therapy (ART), and 6-month clinical outcomes.Results:Between December 2015 to January 2017, 1440 persons were screened at 11 HIV clinics in Kampala, and CRAG+ prevalence was 6.5% (n=94/1440) among adults with a CD4

4. A Prospective Evaluation of a multisite Cryptococcal Screening and Treatment program in HIV clinics in Uganda

AbstractBackground:Cryptococcus is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) is detectable in blood before meningitis onset, and predicts death. CrAg screening amongst those with advanced HIV, and treatment of those CrAg+ with fluconazole has demonstrated survival benefit. However, implementation and widespread uptake have been slow outside of clinical trials.Methods:We designed a CrAg screening program for routine care that incorporated intensive education and training of clinic staff. We evaluated programmatic implementation, including time to initiation of fluconazole, time to initiation of antiretroviral therapy (ART), and 6-month clinical outcomes.Results:Between December 2015 to January 2017, 1440 persons were screened at 11 HIV clinics in Kampala, and CRAG+ prevalence was 6.5% (n=94/1440) among adults with a CD4

5. Absence of Cerebrospinal Fluid Pleocytosis in Tuberculous Meningitis is a Common Occurrence in HIV Co-infection and a Predictor of Poor Outcomes

Cryptococcal meningitis is the most common form of adult meningitis in many regions that have a high prevalence of human immunodeficiency virus (HIV) infection and accounts for 10 to 20% of all HIV-related deaths, with more than 100,000 deaths each year. This high burden is driven by a high case…

Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia and meningitis worldwide. In the majority of cases, GBS is transmitted vertically from mother to neonate, making maternal vaginal colonisation a key risk factor for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of the female genitourinary tract, and the causative agent of vaginal thrush. Carriage of C. albicans has been shown to be an independent risk factor for vaginal colonisation by GBS. However, the nature of interactions between these two microbes is poorly understood. This study provides evidence of a reciprocal, synergistic interplay between GBS and C. albicans that may serve to promote their co-colonisation of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515 (Ia) are shown to physically interact with C. albicans, with bacteria exhibiting tropism for candidal hyphal filaments. This interaction enhances association levels of both microbes with vaginal epithelial cell line VK2/E6E7. The ability of GBS to co-associate with C. albicans is dependent upon expression of hyphal-specific adhesin Als3. In turn, expression of GBS antigen I/II family adhesins (Bsp polypeptides) facilitates this co-association and confers upon surrogate Lactococcus lactis the capacity to exhibit enhanced interactions with C. albicans on vaginal epithelium. As genitourinary tract colonisation is an essential first step in the pathogenesis of GBS and C. albicans, the co-association mechanism reported here may have important implications for risk of disease involving both of these pathogens.

8. CSF Reference Values Help Detect Meningitis in Infants Up to 2 Months Old

Objectives
Diagnosis of Tuberculous Meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and Clinical Prediction Rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic.
Methods
We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model we developed a score‐based CPR. We assessed its internal validity and diagnostic performance.
Results
Of 155 analyzed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10‐500 cells in CSF and adenosine deaminase ≥ 6 U/L in CSF. It classifies patients into high, moderate or low score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high or low score group, permitting prompt decision making. In patients in the high score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity.
Conclusion
This CPR could support decision‐making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact is necessary before application in other settings.
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